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1.
Cureus ; 16(3): e55879, 2024 Mar.
Article En | MEDLINE | ID: mdl-38595886

Combined spinal-epidural anaesthesia is an excellent technique for providing intraoperative and postoperative analgesia in patients undergoing total knee arthroplasty. Epidural catheters threaded through a Tuohy needle with a cephalad needle bevel orientation follow a winding pattern within the epidural space. Caudal or downward migration of an epidural catheter may lead to unsatisfactory anaesthesia and epidural failure. Colour flow Doppler sonography is emerging as an effective technique to determine the epidural catheter tip position. We report an interesting case of caudal migration of a lumbar epidural catheter confirmed by colour flow Doppler ultrasound.

2.
Sci Rep ; 12(1): 12050, 2022 Jul 14.
Article En | MEDLINE | ID: mdl-35835974

Tropospheric Biennial Oscillation (TBO) is characterized by a tendency for a relatively stronger monsoon to be followed by a relatively weaker one (positive) or vice-versa (negative). This study examines the distribution of different convective systems occurring during TBO phases over the Indian monsoon region. During negative TBO phase, convection is preferential over the Arabian Sea (AS), whereas during positive TBO phase, it is favoured over the land areas and Bay of Bengal (BoB). The isolated shallow convection (ISC) is dominated over the AS and Indian west coast during negative TBO years. A relatively stable environment (statically) capped with drier mid-troposphere results in abundant ISC over the AS. Broad stratiform rain (BSR) dominates over the central and east coast of India, BoB and Myanmar coast during positive TBO years and wide convective core (WCC) are present along the orographic regions, i.e., Myanmar coast and Western Ghats during negative TBO phase. The anomalous easterlies induced by the upper-ocean temperature gradient interact with the mean monsoon winds during positive TBO to provide pathways for developing BSR echoes. The deep-wide convection (DWC) are higher along the Himalayan foothills during positive TBO years. The moist low-level flow from the AS is trapped by dry mid-level flow from high latitudes, resulting in orographic lifting along the Himalayan foothills and form DWC.

3.
Sci Rep ; 11(1): 14103, 2021 Jul 08.
Article En | MEDLINE | ID: mdl-34238946

Diurnal variation of convective storms (CSs) during monsoon season and associated physical mechanisms are significantly important for accurate forecast of short-time and extreme precipitation. The diurnal cycle of CSs is investigated using ground-based X-band radar, Tropical Rainfall Measuring Mission Precipitation Radar, and reanalysis data during the summer monsoon (June-September of 2014) over complex mountain terrain of Western Ghats, India. Diurnally, CSs show a bimodal distribution in the coastal areas, but this bimodality became weak along the upslope regions and on the mountain top. The first occurrence mode of CSs is in the afternoon-evening hours, while the second peak is in the early-morning hours. The diurnal cycle's intensity varies with location, such that it reaches maximum in the afternoon-evening hours and early morning on the mountain top and coastal areas, respectively. Two possible mechanisms are proposed for the observed diurnal variation in CSs (a) the radiative cooling effect and (b) the surface wind convergence induced by the interaction between land-sea breeze, local topography and large-scale monsoon winds. It is also observed that the CSs developed on the mountain top during afternoon-evening hours are deeper than those along the coast. The higher moisture in the lower- and mid-troposphere, higher instability and strong upward motion facilitate deeper CSs during afternoon-evening hours.

4.
Indian J Dent Res ; 31(2): 305-311, 2020.
Article En | MEDLINE | ID: mdl-32436913

BACKGROUND: Abfraction is a loss of tooth structure along the gingival margin and manifests with different clinical appearances. It has multifactorial etiology and may occur due to normal and abnormal tooth function and may also be accompanied by pathological wear, such as abrasion and erosion. The theory behind the abfraction is that the tooth flexure in the cervical area is caused due to occlusal compressive forces and tensile stresses. This results in the fractures in the hydroxyapatite (HA) crystals. It is also caused by the low packing density of the Hunter-Schreger band (HSB) at the cervical area. Unfortunately, there is a lack of evidence regarding the outcome of abfraction with or without intervention. The aim of this review is to collect clinical information from the literature and discuss the etiology, pathogenesis, clinical representation, and management. Also, search databases for clinical studies that describe the role of sclerotic dentine in non-carious cervical lesions (NCCLs) are becoming a clinical challenge. METHODS: The literature was searched that described the etiology, pathogenesis, clinical representation, and management of the abfraction lesions. Also, a specific question regarding the formation of sclerotic dentin in the NCCL lesion was described and searched for evidence that challenges etching, bonding, and successfully restoring NCCLs. The databases PUBMED, SCOPUS, MEDLINE, WEB of SCIENCE, and EMBASE were searched using the key terms. The inclusion criteria were the randomized controlled clinical trial, cohort studies, and cross-sectional studies that aimed at determining the role of sclerotic dentine in NCCLs and its effect on etching, bonding. RESULTS: One clinical study was retrieved according to the PRISMA flowchart and PICO format. The longer etching time, total-etch adhesive system, and EDTA pre-treatment of the sclerotic dentin of cervical wedge-shaped defects could improve the bonding strength in lesions like NCCL's. CONCLUSION: In conclusion, clinical challenges that occur due to NCCLs are better managed by a proper understanding of factors like etiopathogenesis, ultra-structure of enamel, and dentine and their effect on the bonding of restorations of the tooth.


Tooth Cervix , Tooth Diseases , Cross-Sectional Studies , Dental Enamel , Dentin , Humans
5.
Ann Maxillofac Surg ; 9(2): 340-344, 2019.
Article En | MEDLINE | ID: mdl-31909012

BACKGROUND: It has been reported that 20%-60% of all people injured in road traffic accidents (RTAs) tend to have some form of maxillofacial injury. Mangalore city, Karnataka State, India, traffic police has enforced the law to wear helmets to tackle the problem. The outcome of the initiative till date was not measured. Therefore, the objective of the study was to assess the prevalence of maxillofacial injuries among the victims of motorized two-wheeler RTAs, following the passing of the helmet law. MATERIALS AND METHODS: The study was conducted at the Accident and Emergency Department of K.S. Hegde Medical College and Hospital and at the Department of Oral and Maxillofacial Surgery, A.B. Shetty Memorial Institute of Dental Sciences, Nitte (Deemed to be University), Mangalore, Karnataka, India. The inclusion criteria were the patients who had two-wheeler accidents during the time period of 2016-2017 was collected. The data related to age, gender, helmet wearing, diagnosis, and type of orthopedic injuries was included. A descriptive statistics was calculated along with 95% confidence interval; correlation coefficient and odds ratio using STATA software. RESULTS: A total of N = 347 individuals were included in the study. The mean age of the individuals was 33.7 (2-85) years, and the median age was 32 years. 81.55% (N = 283) were male and 18.44% (N = 64) were female. Among the individuals, 51.5% (N = 179) were not wearing helmets and 44.38% (N = 154) of them were males. A total of 25.07 (N = 87) individuals had orthopedic injuries and 16.42% (N = 57) individuals had orthopedic injuries who were not wearing helmets. CONCLUSION: Under the limitations of the study, we conclude that majority of the two-wheelers are not wearing helmets. This study has demonstrated that the impact of wearing helmet on occurrence of craniofacial and orthopedic injuries is less.

6.
Oncogene ; 35(48): 6262-6269, 2016 12 01.
Article En | MEDLINE | ID: mdl-27157617

Helicobacter pylori (H. pylori) is the strongest identified risk factor for gastric cancer, the third most common cause of cancer-related death worldwide. An H. pylori constituent that augments cancer risk is the strain-specific cag pathogenicity island, which encodes a type IV secretion system (T4SS) that translocates a pro-inflammatory and oncogenic protein, CagA, into epithelial cells. However, the majority of persons colonized with CagA+ H. pylori strains do not develop cancer, suggesting that other microbial effectors also have a role in carcinogenesis. Toll-like receptor 9 (TLR9) is an endosome bound, innate immune receptor that detects and responds to hypo-methylated CpG DNA motifs that are most commonly found in microbial genomes. High-expression tlr9 polymorphisms have been linked to the development of premalignant lesions in the stomach. We now demonstrate that levels of H. pylori-mediated TLR9 activation and expression are directly related to gastric cancer risk in human populations. Mechanistically, we show for the first time that the H. pylori cancer-associated cag T4SS is required for TLR9 activation and that H. pylori DNA is actively translocated by the cag T4SS to engage this host receptor. Activation of TLR9 occurs through a contact-dependent mechanism between pathogen and host, and involves transfer of microbial DNA that is both protected as well as exposed during transport. These results indicate that TLR9 activation via the cag island may modify the risk for malignancy within the context of H. pylori infection and provide an important framework for future studies investigating the microbial-epithelial interface in gastric carcinogenesis.


Bacterial Proteins/metabolism , Helicobacter Infections/metabolism , Helicobacter Infections/microbiology , Helicobacter pylori/physiology , Toll-Like Receptor 9/metabolism , Type IV Secretion Systems , Bacterial Proteins/genetics , Biological Transport , Carcinogenesis , DNA, Bacterial/genetics , DNA, Bacterial/metabolism , Helicobacter Infections/complications , Humans , Mutation , Stomach Neoplasms/etiology
7.
Plant Cell Environ ; 38(5): 867-77, 2015 May.
Article En | MEDLINE | ID: mdl-24689776

Perennial plants growing at high latitudes synchronize growth and dormancy to appropriate seasons by sensing environmental cues. Autumnal growth cessation, bud set and dormancy induction are commonly driven by the length of photoperiod and light quality, and the responses are modified by temperature. However, although ultraviolet (UV)-B radiation is well known to affect plant growth and development, information on the effects on bud phenology is scarce. We examined the separate and combined effects of enhanced temperature and UV-B on autumnal bud set and spring bud break in female and male clones of Populus tremula in an outdoor experiment in Joensuu, Eastern Finland. Enhancements of UV-B and temperature were modulated to +30% and +2 °C, respectively, from June to October 2012. Enhanced UV-B accelerated bud set, while increased temperature delayed it. For both UV-B and temperature, we found sex-related differences in responsiveness. Temperature increase had a stronger delaying effect on bud maturation in male compared with female clones. Also, male clones were more responsive to UV-B increase than female clones. Increasing autumnal temperature enhanced bud break in spring for both sexes, while UV-B enhanced bud break in male clones. In conclusion, we found that UV-B affected phenological shifts in P. tremula, and that temperature and UV-B affected genders differently.


Populus/growth & development , Populus/radiation effects , Seasons , Temperature , Ultraviolet Rays
8.
Indian J Dent Res ; 24(6): 736-41, 2013.
Article En | MEDLINE | ID: mdl-24552936

OBJECTIVE: Evaluate the changes in alveolar bone as a result of maxillary and mandibular incisor retraction in patients with bimaxillary protrusion by means of using lateral cephalograms and computed tomography (CT) scans and to investigate any occurrence of bony defects like dehiscence and fenestration. SUBJECTS AND METHODS: Ten patients (age 15 ± 3 years) with bimaxillary protrusion treated by extraction of four first premolars were investigated by lateral cephalograms and CT scans during pre-treatment (T1) and after 3 months of completion of incisor retraction (T2). The labial and lingual cortex of all the incisors were assessed on the CT scan with measurements taken at site adjacent to widest point of the labiolingual root in three slices separated by 3 mm at crest level (S1), mid root level (S2), and apical level (S3). RESULT: In the mandibular arch, after lingual movement of the incisors, the bone labial to the anterior teeth decreased in thickness at the coronal level of the left lateral and left central incisors. Left lateral incisor showed significant changes in all the three levels. In the maxilla the change in the labial bone thickness was not statistically significant. Lingual bone of all the incisors showed significant changes in S1 level and S3 levels. Few patients demonstrated bone dehiscence that was not visible macroscopically or cephalometrically. CONCLUSIONS: When incisors are retracted, the risk of adverse effect is present. This must be carefully monitored to avoid negative iatrogenic effects. This study needs follow up after 6 months or 1 year after completion of the orthodontic treatment to assess the long-term consequences.


Alveolar Process/anatomy & histology , Cephalometry , Orthodontics , Tomography, X-Ray Computed , Adolescent , Alveolar Process/diagnostic imaging , Child , Humans
9.
Ayu ; 33(4): 499-504, 2012 Oct.
Article En | MEDLINE | ID: mdl-23723666

We describe here three patients with the Alzheimer's Disease (AD) whose behavioral symptoms were improved remarkably as a result of the turmeric treatment, which is the traditional Indian medicine. Their cognitive decline and Behavioral and Psychological Symptoms of Dementia (BPSD) were very severe. All three patients exhibited irritability, agitation, anxiety, and apathy, two patients suffer from urinary incontinence and wonderings. They were prescribed turmeric powder capsules and started recovering from these symptoms without any adverse reaction in the clinical symptom and laboratory data. After 12 weeks of the treatment, total score of the Neuro-Psychiatric Inventory-brief questionnaire decreased significantly in both acuity of symptoms and burden of caregivers. In one case, the Mini-Mental State Examination (MMSE) score was up five points, from 12/30 to 17/30. In the other two cases, no significant change was seen in the MMSE; however, they came to recognize their family within 1 year treatment. All cases have been taking turmeric for more than 1 year, re-exacerbation of BPSD was not seen. The present cases suggest a significant improvement of the behavioral symptoms in the AD with the turmeric treatment, leading to probable benefit of the use of turmeric in individuals with the AD with BPSD.

10.
Ars pharm ; 52(1): 5-11, ene.-mar. 2011. ilus, tab, graf
Article En | IBECS | ID: ibc-88800

The study involves the condensation of acylimidazole derivatives of acaclofenac (AC) with dextran 10,000 and 20,000 to obtain aceclofenac-dextran prodrugs AC10 and AC20 respectively with an aim to improve aqueous solubility, increase therapeutic efficiency and reduce the gastrointestinal side effects. The structure of synthesized prodrugs was confirmed by IR and NMR spectroscopy. The molecular weight was determined by Mark-Howink Sakurada equation and the degree of substitution was obtained as 13.3 and 16 % for the prodrugs. In vitro hydrolysis carried out in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF) showed faster hydrolysis in SIF and SCF. The percentage anti-inflammatory activity of AC was found as 49.56 whereas an improved value of 56.44 and 61.82 % were obtained for AC10 and AC20 respectively. The prodrugs showed improved analgesia and reduced ulcerogenicity than aceclofenac, thereby proving to be better in action than the parent drug(AU)


El estudio se centra en la condensación de acilimidazoles derivados de aceclofenaco (AC) con dextrano 10.000 y 20.000 para obtener los profármacos de aceclofenaco-dextrano AC10 y AC20, respectivamente, con el objetivo de mejorar la hidrosolubilidad, aumentar la eficacia terapéutica y reducir los efectos secundarios gastrointestinales. La estructura de los profármacos sintetizados se ha confirmado a través de espectroscopia IR y RMN. El peso molecular ha sido determinado a través de la ecuación de Mark-Houwink-Sakurada y se ha obtenido un grado de sustitución de 13,3 y 16% para los profármacos. La hidrólisis in vitro llevada a cabo en fluido gástrico simulado (FGS), fluido intestinal simulado (FIS) y fluido colónico simulado (FCS) ha mostrado una hidrólisis más rápida en FIS y FCS. De ello ha resultado un porcentaje de actividad antiinflamatoria de AC de 49,56, mientras que para AC10 y AC20 se ha obtenido un valor aumentado de 56,44 y 61,82% respectivamente. Los profármacos han mostrado una mejor analgesia y una menor ulcerogenicidad que el aceclofenaco, por lo que se demuestra que su acción es mejor que la del fármaco base(AU)


Humans , Male , Female , Prodrugs/analysis , Prodrugs/classification , Prodrugs/history , Prodrugs/therapeutic use , Hydrolysis , Hydrolysis/radiation effects , Histology, Comparative/history , Histology, Comparative/statistics & numerical data , Histology, Comparative/standards , Prodrugs/economics , Prodrugs/pharmacology , Prodrugs/supply & distribution , Prodrugs/standards , Histology, Comparative/classification , Histology, Comparative/ethics , Histology, Comparative/trends
11.
Contemp Clin Dent ; 2(4): 376-80, 2011 Oct.
Article En | MEDLINE | ID: mdl-22346172

The use of functional jaw orthopedics, at the correct time during growth, can ultimately result in malocclusion patients achieving a broad beautiful smile, an excellent functional occlusion, a full face with a beautiful jaw line and lateral profile. Following is a case report of a young growing individual with mandibular retrognathia. Treatment was planned in two stages with the use of twin block during the first phase for correction of skeletal malocclusion and forward positioning of the mandible, followed by the second phase of fixed pre-adjusted edgewise orthodontic appliance for camouflaging the remaining skeletal discrepancy and achieving a stable harmonious occlusion.

12.
Clin Microbiol Infect ; 16(4): 369-78, 2010 Apr.
Article En | MEDLINE | ID: mdl-19456839

The C-terminus of the Helicobacter pylori CagA protein is polymorphic, bearing different EPIYA sequences (EPIYA-A, B, C or D), and one or more CagA multimerization (CM) motifs. The number of EPIYA-C motifs is associated with precancerous lesions and gastric cancer (GC). The relationship between EPIYA, CM motifs and gastric lesions was examined in H. pylori-infected Colombian patients from areas of high and low risk for GC. Genomic DNA was extracted from H. pylori strains cultured from gastric biopsies from 80 adults with dyspeptic symptoms. Sixty-seven (83.8%) of 80 strains were cagA positive. The 3' region of cagA was sequenced, and EPIYA and CM motifs were identified. CagA proteins contained one (64.2%), two (34.3%) or three EPIYA-C motifs (1.5%), all with Western type CagA-specific sequences. Strains with one EPIYA-C motif were associated with less severe gastric lesions (non-atrophic and multifocal atrophic gastritis), whereas strains with multiple EPIYA-C motifs were associated with more severe lesions (intestinal metaplasia and dysplasia) (p <0.001). In 54 strains, the CM motifs were identical to those common in Western strains. Thirteen strains from the low-risk area contained two different CM motifs: one of Western type located within the EPIYA-C segment and another following the EPIYA-C segment and resembling the CM motif found in East Asian strains. These strains induced significantly shorter projections in AGS cells and an attenuated reduction in levels of CagA upon immunodepletion of SHP-2 than strains possessing Western/Western motifs. This novel finding may partially explain the difference in GC incidence in these populations.


Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Helicobacter Infections/complications , Helicobacter pylori/genetics , Precancerous Conditions/microbiology , Stomach Neoplasms/microbiology , Adult , Amino Acid Sequence , Antigens, Bacterial/chemistry , Antigens, Bacterial/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Colombia , Gastric Mucosa/metabolism , Gastric Mucosa/microbiology , Helicobacter pylori/isolation & purification , Helicobacter pylori/metabolism , Humans , Male , Middle Aged , Molecular Sequence Data , Polymorphism, Genetic , Precancerous Conditions/metabolism , Precancerous Conditions/pathology , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology
13.
J Cytol ; 26(4): 158-60, 2009 Oct.
Article En | MEDLINE | ID: mdl-21938184

Primary intracystic squamous cell carcinoma (SCC) of the breast is an extremely rare entity and has a low incidence in comparison with other breast cancers. We report a rare case of primary intracystic SCC in a 45-year-old woman who presented with a cystic lump in the right breast. Cytological smears of the fluid aspirated from the breast tumor revealed malignant squamous cells dispersed in single and occasional groups along with numerous cyst macrophages, suggesting cystic SCC. Histological study of the mastectomy specimen confirmed the diagnosis of primary intracystic SCC. Although the presence of abundant foamy macrophages in the background of fine needle aspiration cytology smears of the breast suggest benign breast lesion, when associated with malignant squamous cells, these suggest cystic primary SCC or metastatic SCC. The primary SCC should not be confused with metaplastic change in other breast carcinomas.

14.
Lipids ; 42(3): 291-6, 2007 Apr.
Article En | MEDLINE | ID: mdl-17393233

A novel phosphonium salt methodology was utilized for the first time to synthesize 1,3-, and 1,2-diphosphatidylglycerol. Optically active 1,2-di-O-acyl-sn-glyceryl phosphate was coupled with unprotected glycerol in the presence of pyridiniumbromide perbromide and triethylamine to yield, after final removal of phosphate protecting group, the title compounds. The 1,2-diphosphatidylglycerol (1,2-isomer of cardiolipin) may be a member of a new class of phospholipids for industrial applications similar to other phosphocholines.


Cardiolipins/chemistry , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray Ionization , Spectroscopy, Fourier Transform Infrared
15.
BJOG ; 114(3): 271-8, 2007 Mar.
Article En | MEDLINE | ID: mdl-17217359

OBJECTIVE: The objective of this study was to determine if a repeat dose of misoprostol following mifepristone or a single dose of misoprostol increases the efficacy of medical termination of pregnancy. DESIGN: Randomised, placebo controlled trial. SETTING: K.E.M. Hospital, Pune, India, and the Health Centre, Larsen and Toubro Limited, Mumbai, India. SAMPLE: A total of 300 women seeking an abortion with amenorrhoea of 8 weeks or less. Methods Women were randomised to receive one or two doses of 400 microgram oral misoprostol at the clinic 48 hours after administration of 200 mg mifepristone. Main outcome measure Complete abortion without surgical intervention. Results The repeat administration of misoprostol 400 microgram improved the complete abortion rate from 86 to 92% and significantly reduced the rate of continuing pregnancy from 7 to 1%. Almost all the women who were administered the additional dose of misoprostol were either very satisfied (58%) or satisfied (37%) with the method. Conclusion While an additional oral dose of 400 microgram misoprostol did not significantly increase the rate of complete abortion without surgical intervention, the additional dose did significantly reduce the rate of continuing pregnancies without compromising the acceptability and ease of use of the method.


Abortifacient Agents, Nonsteroidal/administration & dosage , Abortifacient Agents, Steroidal/administration & dosage , Abortion, Induced/methods , Mifepristone/administration & dosage , Misoprostol/administration & dosage , Adult , Amenorrhea/etiology , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Patient Satisfaction , Pregnancy , Treatment Outcome
16.
Int J Oncol ; 27(5): 1177-85, 2005 Nov.
Article En | MEDLINE | ID: mdl-16211211

Trans arachidonic acid isomers (trans-AA) constitute a new group of trans fatty acids (trans-FA) generated in vivo via endogenous cis-trans isomerization stimulated by the NO2 radical. Because both NO2 and trans-FA have been implicated as causative factors in cancer, we studied the effect of the trans-AA isomers on proliferation and viability of human promyelocytic (HL-60) cells. The four trans arachidonic (trans-AA) acid isomers synthesized by us have been presently tested with respect to their competence to affect the proliferation and viability of human promyeolocytic HL-60 cells in culture. The data demonstrate that one of the isomers, 5,6-trans-AA, showed distinct activity by targeting cell progression through the cell cycle and inducing apoptosis. The effects were time- and concentration-dependent: the cytostatic effect of 5E-AA was observed at 10 microM following 72 h of treatment. This effect was manifested as a perturbation of cell progression through G1 phase, indicating the 'on' activation of the G1 checkpoint as evidenced by the flow- and laser scanning-cytometry techniques. Apoptotic cells were identified by comparison of their morphology, DNA fragmentation, caspase activation and collapse of mitochondrial potential with control cells. These observations suggested that 5E-AA induced a mitochondrial pathway of apoptosis. There was no evidence of cell-cycle phase specificity in induction of apoptosis by 5E-AA, as the cells showing highly fragmented DNA or caspase-3 activation were distributed in all phases of the cycle. The data suggest that 5E-AA may have at least two targets: one that is cell-cycle specific and associated with the observed arrest in the G1 phase and another, unrelated to the cell cycle, which is responsible for triggering apoptosis indiscriminately, regardless of cycle phase I.


Apoptosis/drug effects , Arachidonic Acid/pharmacology , G1 Phase/drug effects , DNA Damage , HL-60 Cells , Humans , Isomerism , Mitochondria/drug effects , Mitochondria/physiology
17.
Lipids ; 39(6): 595-600, 2004 Jun.
Article En | MEDLINE | ID: mdl-15554161

A new approach is described for the synthesis of the cardiolipin family of phospholipids that uses phosphonium salt methodology. The method involves the reaction of 2-O-protected glycerol with a trialkyl phosphite derived from 1,2-diacylsn-glycerol in the presence of pyridinium bromide perbromide and triethylamine to afford the phosphoric triesters. The synthesis involves three steps and allows the preparation of a wide range of cardiolipins with different substitution patterns and chain lengths, including unsaturated derivatives. The use of inexpensive protecting groups and the ease of purification facilitate this synthetic route and allow its scale-up in a higher overall yield (72%) than the literature methods.


Cardiolipins/chemistry , Methods , Organophosphonates/chemistry , Organophosphorus Compounds/chemistry
19.
J Biol Chem ; 278(37): 35629-35, 2003 Sep 12.
Article En | MEDLINE | ID: mdl-12832407

Diacylglycerol kinase alpha (DAGK alpha), like all type I DAGKs, has calcium regulatory motifs that act as negative regulators of enzyme activity and localization. Accordingly, DAGK alpha is activated by phospholipase C-coupled receptors in a calcium-dependent manner. One of the first functions attributed to DAGK alpha in lymphocytes was that of regulating interleukin 2-induced cell cycle entry. Interleukin-2 nonetheless exerts its action in the absence of cytosolic calcium increase. We have studied alternative receptor-derived signals to explain calcium-independent DAGK alpha activation, and show that DAGK alpha is stimulated by Src-like kinase-dependent phosphoinositide 3 kinase (PI3K) activation in lymphocytes. Our results demonstrate that, in vivo, the increase in cellular levels of PI3K products is sufficient to induce DAGK alpha activation, allowing DAGK alpha relocation to the intact lymphocyte plasma membrane. This activation is isoform-specific, because other type I DAGKs are not subject to this type of regulation. These studies are the first to describe a pathway in which, in the absence of receptor-regulated calcium increase, DAGK alpha activation and membrane localization is a direct consequence of PI3K activation.


Diacylglycerol Kinase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Animals , Binding Sites , Cell Line , Diacylglycerol Kinase/genetics , Enzyme Activation , Humans , Interleukin-2/pharmacology , Mice , Peptide Fragments/metabolism , Plasmids , Recombinant Proteins/metabolism , Transfection
20.
Am J Physiol Heart Circ Physiol ; 284(1): H337-49, 2003 Jan.
Article En | MEDLINE | ID: mdl-12388250

Epoxyeicosatrienoic acids (EETs) are endothelium-derived eicosanoids that activate potassium channels, hyperpolarize the membrane, and cause relaxation. We tested 19 analogs of 14,15-EET on vascular tone to determine the structural features required for activity. 14,15-EET relaxed bovine coronary arterial rings in a concentration-related manner (ED(50) = 10(-6) M). Changing the carboxyl to an alcohol eliminated dilator activity, whereas 14,15-EET-methyl ester and 14,15-EET-methylsulfonimide retained full activity. Shortening the distance between the carboxyl and epoxy groups reduced the agonist potency and activity. Removal of all three double bonds decreased potency. An analog with a Delta8 double bond had full activity and potency. However, the analogs with only a Delta5 or Delta11 double bond had reduced potency. Conversion of the epoxy oxygen to a sulfur or nitrogen resulted in loss of activity. 14(S),15(R)-EET was more potent than 14(R),15(S)-EET, and 14,15-(cis)-EET was more potent than 14,15-(trans)-EET. These studies indicate that the structural features of 14,15-EET required for relaxation of the bovine coronary artery include a carbon-1 acidic group, a Delta8 double bond, and a 14(S),15(R)-(cis)-epoxy group.


8,11,14-Eicosatrienoic Acid/analogs & derivatives , 8,11,14-Eicosatrienoic Acid/chemistry , 8,11,14-Eicosatrienoic Acid/pharmacology , Coronary Vessels/drug effects , Coronary Vessels/physiology , Vasodilator Agents/chemistry , Vasodilator Agents/pharmacology , Animals , Arteries , Cattle , In Vitro Techniques , Structure-Activity Relationship , Vasodilation
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